Human defense against inflammation and cancer employs a dual response system consisting of both cellular and humoral immune response. The cellular immune response utilizes lymphoid cells such as lymphocytes and accessory lymphoid cells, and the humoral immune response is provided by antibodies which recognize unique molecular determinants expressed in inflammation and cancer cells.
Autoimmune diseases are a class of inflammation-associated disorders characterized by immunogenic reaction against normal cellular constituents. Most autoimmune antigenicity is correlated with four small nuclear ribonucleoprotein polypeptides (snRNPs): snRNP B, B', D, and E. For example, antibodies specific for recognizing snRNPs are expressed ubiquitously in patients with lupus erythematosus. In particular, Sm-D is an snRNP autoantigen which is closely associated with rheumatic diseases. Sm-D is a 13.3 kDa protein which exhibits a potential immunoreactive determinant rich in Gly and Arg at its carboxy terminus (Rokeach, L. A. et al. (1988) Proc. Natl. Acad. Sci. 85: 4832-4836; Mitsuda, T. et al. (1992) J. Autoimmun. 5: 277-287).
Cancers or malignant tumors are characterized by continuous cell proliferation and cell death. Cancer cells have been shown to exhibit unique gene expression, and dozens of cancer-specific genetic markers, tumor antigens, have been identified. P35B, a tumor rejection antigen, was first identified in mouse. A point mutation in the P35B gene elicits a cytolytic T lymphocyte response but no detectable antibody response (Szikora, J. P. et al. (1990) EMBO J. 9:1041-1050). A human homolog of P35B, FX, is a homodimeric NADP(H)-binding protein of 68 kDa. FX acts as a combined epimerase and NADPH-dependent reductase in converting GDP-4-keto-6-D-deoxymannose to GDP-L-fucose (Tonetti, M. et al. (1996) J. Biol. Chem. 271: 27274-27279). GDP-L-fucose is the substrate of several facosyl-transferases involved in the biosysthesis of blood group ABH antigenic determinants. GDP-L-fucose is also utilized in synthesizing fucosylated glycoproteins and glycolipids which function in cell adhesion and recognition (Springer, T. A. and Lasky, L. A. (1991) Nature 329: 196-197; Brandley, B. K. et al. (1990) Cell 63: 861-863; and Feizi, T. and Childs, R. A. (1987) Biochem. J. 245: 1-11).
The discovery of two new human antigens and the polynucleotides encoding them satisfies a need in the art by providing new compositions which are usefull in the diagnosis, prevention and treatment of inflammation and disorders associated with cell proliferation and apoptosis.